This vaccine program is comprised of a group of interactive investigators with a long standing commitment to the AIDS vaccine research agenda. Our V3 loop and gp41 peptides conjugated to PPD and to M. tuberculosis (TB) derived protein carriers have induced among other neutralizing antibodies to primary isolates in humans and in animals. New conserved glycoproteins in the V1/V2 regions appear also to induce broad neutralization. The overall goal of this program is to exploit our experience to develop: 1) improved preventative peptide AIDS vaccines to include but not limited to the V3 loop and gp41 cocktails. The flexibility of our peptide vaccine development will allow us to rapidly and inexpensively incorporate new epitopes such as those related to HIV-1 co-receptors. 2) Dr. Pinter will add a new dimension to this program by conjugating to PPD highly conserved epitopes of the V1/V2 domain of gp120 which mediate potent neutralization of M tropic primary HIV isolates. 3) Dr. Goldstein's human CD4/CCR5 transgenic mouse will serve as an in vivo model for all vaccine constructs. In addition the HIV infected SCID- hu mice (core) will provide an in vivo system to test the biological function of neutralizing antibodies generated in animals and in humans. This collaborative project focuses on preventative vaccines but will utilize also therapeutic vaccination as a model for preventative vaccines. In limited clinical trials out PPD V3 pentapeptide conjugate vaccine induced in HIV+PPD+ subjects high titers of primary isolate neutralizing antibodies and reduced plasma viral loads. In collaboration with Dr. Ali Javadian, we will evaluate the potential of a polyepitopic V3, gp41 peptide-PPD-conjugate vaccine to induce neutralizing antibodies and to reduce viral loads in BCG immunized HIV+ chimps. This consortium will continue to collaborate with its commercial partners, ThereGuide and the Swiss Serum and Vaccine Institute (SSVI) to prepare GLP vaccine available for clinical trials. Clinical trials will initially continue abroad (Israel; Brazil) where a large PPD+ cohort is readily available. Future studies in the US will be designed with NIAID program staff.